The broad focus of our research is to understand how their gigantic size and unrivaled morphological complexity endow neurons with unique means to spatially segregate cellular processes that are not intrinsically compartmentalized in simpler cells, and hence tune their membrane composition and properties on a synapse-by-synapse basis.
We are particularly interested in the mechanisms that enable neurons to locally produce and traffic cell-adhesion molecules and synaptic receptors to functionalize specific segments of dendrites or synapses during neuronal development and synaptic plasticity.
Our recent work indicates that the spatial segregation of protein synthesis and secretory processing in the soma versus dendrites allows neurons to exploit multiple pathways to diversify the properties (e.g. stability, desensitization) of surface membrane proteins. More specifically, we found that, as a result of unconventional secretory processing, hundreds of key surface-expressed neurotransmitter receptors, voltage-gated ion channels and synaptic adhesion proteins display glycosylation profiles that are typically associated with immature proteins before their export to the cell surface. This so-called core-glycosylation is associated with a faster protein turnover and is regulated by synaptic activity, unraveling a novel mechanism controlling the composition and plasticity of the neuronal membrane.
We use and develop advanced live-cell imaging methods, transgenic mice and biochemical approaches to study membrane protein processing and glycosylation in cultured neurons and brain slices. Our main objectives for the short and midterm future are: 1) to assess the contribution of unconventional N-glycans to dendritic growth and synaptic signaling; and 2) to determine the impact of local protein synthesis on the N-glycosylation, surface expression, stability and regulability of synaptic proteins during synaptic plasticity.
5 main publications
Alvarez-Castelao B, Schanzenbächer CT, Hanus C, Glock C, Tom Dieck S, Dörrbaum AR, Bartnik I, Nassim-Assir B, Ciirdaeva E, Mueller A, Dieterich DC, Tirrell DA, Langer JD, Schuman EM. Cell-type-specific metabolic labeling of nascent proteomes in vivo. Nat Biotechnol. 2017 Nov 6. doi: 10.1038/nbt.4016.
Bowen AB, Bourke AM, Hiester BG, Hanus C, Kennedy MJ. Golgi-independent secretory trafficking through recycling endosomes in neuronal dendrites and spines. Elife. 2017 Sep 6;6. pii: e27362. doi: 10.7554/eLife.27362.
Hanus C#, Geptin H, Tushev G, Garg S, Alvarez-Castelao B, Sambandan S, Kochen L, Hafner AS, Langer J, Schuman EM#. Unconventional secretory processing diversifies neuronal ion channel properties. eLife (eLife-20609) DOI 10.7554/eLife.20609. #Corresponding authors.
Hanus C#, Kochen L, tom Dieck S, Racine V, Sibarita JB, Schuman EM, Ehlers MD# (2014). Synaptic Control of Early Secretory Trafficking in Dendrites. Cell Reports, 7(6):1771-8. # Corresponding authors.
Cui-Wang T*, Hanus C*, Cui T, Helton TD, Bourne J, Watson DJ, Harris KM, Ehlers MD (2012). Local Zones of ER Complexity Confine Cargo in Neuronal Dendrites. Cell, 148(1-2):309-21. *Equal contribution.